Identification, Prediction and Data Analysis of Noncoding RNAs: A Review.

BACKGROUND: Noncoding RNAs (ncRNAs) which play an important role in various cellular processes are important in medicine as well as in drug design strategies. Different studies have shown that ncRNAs are dis-regulated in cancer cells and play an important role in human tumorigenesis. Therefore, it is important to identify and predict such molecules by experimental and computational methods, respectively. However, to avoid expensive experimental methods, computational algorithms have been developed for accurately and fast prediction of ncRNAs. OBJECTIVE: The aim of this review was to introduce the experimental and computational methods to identify and predict ncRNAs structure. Also, we explained the ncRNA's roles in cellular processes and drugs design, briefly. METHOD: In this survey, we will introduce ncRNAs and their roles in biological and medicinal processes. Then, some important laboratory techniques will be studied to identify ncRNAs. Finally, the state-of-the-art models and algorithms will be introduced along with important tools and databases. RESULTS: The results showed that the integration of experimental and computational approaches improves to identify ncRNAs. Moreover, the high accurate databases, algorithms and tools were compared to predict the ncRNAs. CONCLUSION: ncRNAs prediction is an exciting research field, but there are different difficulties. It requires accurate and reliable algorithms and tools. Also, it should be mentioned that computational costs of such algorithm including running time and usage memory are very important. Finally, some suggestions were presented to improve computational methods of ncRNAs gene and structural prediction.

Author Correction: Anti-angiogenic drug scheduling optimisation with application to colorectal cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Anti-angiogenic drug scheduling optimisation with application to colorectal cancer.

Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by "normalizing" abnormal tumor vessels and improving drug penetration. Nevertheless, the clinical relevance of this phenomenon is still unclear with several studies over recent years suggesting an opposing relationship. Herein, we sought to develop a new computational tool to interrogate anti-angiogenic drug scheduling with particular application in the setting of colorectal cancer (CRC). Specifically, we have employed a mathematical model of vascular tumour growth which interrogates the impact of anti-angiogenic treatment and chemotherapeutic treatment on tumour volume. Model predictions were validated using CRC xenografts which underwent treatment with a clinically relevant combinatorial anti-angiogenic regimen. Bayesian model selection revealed the most appropriate term for capturing the effect of treatments on the tumour size, and provided insights into a switch-like dependence of FOLFOX delivery on the tumour vasculature. Our experimental data and mathematical model suggest that delivering chemotherapy prior to bvz may be optimal in the colorectal cancer setting.

The microRNA-205-5p is correlated to metastatic potential of 21T series: A breast cancer progression model.

MicroRNA is a class of noncoding RNAs able to base pair with complementary messenger RNA sequences, inhibiting their expression. These regulatory molecules play important roles in key cellular processes including cell proliferation, differentiation and response to DNA damage; changes in miRNA expression are a common feature of human cancers. To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression. These stages are represented by cell lines derived from normal epithelial (H16N2), atypical ductal hyperplasia (21PT), primary in situ ductal carcinoma (21NT) and pleural effusion of a lung metastasis (21MT-1 and 21MT-2). In a global microRNA expression analysis, miR-205-5p was the only miRNA to display an important downregulation in the metastatic cell lines (21MT-1; 21MT-2) when compared to the non-invasive cells (21PT and 21NT). The lower amounts of miR-205-5p found also correlated with high histological grades biopsies and with higher invasion rates in a Boyden chamber assay. This work pinpoints miR-205-5p as a potential player in breast tumor invasiveness.

Delayed graft function and cotrimoxazole.

Acute interstitial nephritis is an infrequent cause of early allograft dysfunction. Prophylactic trimethoprim sulfamethoxazole (cotrimoxazole) is frequently prescribed early in the course of kidney transplantation. Herein we have reported a case of delayed graft function associated with eosinophilia in which the renal biopsy showed interstitial mononuclear infiltrates with abundant eosinophils. An initial methylprednisolone course failed to lower the serum creatinine, but renal function and eosinophilia persistently improved following cotrimoxazole withdrawal and a second course of steroids. Cotrimoxazole acute interstitial nephritis is an infrequent but treatable cause of kidney allograft dysfunction, which should be included in the differential diagnosis of delayed renal allograft function.

Obstructive nephropathy secondary to AA-type amyloidosis in ankylosing spondylitis.

AA-type amyloidosis of the genitourinary tract is a rare phenomenon and few cases are described in the literature. We report a 42-year-old man with ankylosing spondylitis, who developed hematuria, bilateral hydronephrosis, and renal failure caused by AA amyloidosis.

Histological changes in human dental pulp following application of intrusive and extrusive orthodontic forces.

The aim of this study was to compare the effects of orthodontic extrusive and intrusive forces on histological changes of the human dental pulp. In this clinical trial, 52 sound upper first premolars from 26 patients scheduled for extraction for orthodontic reasons were selected. They were divided into 2 groups, based on the time intervals for histological evaluation (3 days and 3 weeks). In each group, 10 teeth received orthodontic extrusive forces, 10 teeth underwent intrusive forces, and 6 teeth served as controls. After each period, teeth were extracted and prepared for histological examination under light microscopy and some histological parameters were evaluated. The data were statistically analyzed by Kruskall-Wallis and Mann Whitney tests. Of the parameters evaluated, just vacuolization and disruption of the odontoblastic layer showed statistically significant differences between the control group and both of the experimental groups in each test period (P < 0.05). Additionally, there was no significant difference between 3-day and 3-week intervals in each experimental group, except for fibrosis in the extrusive group which significantly increased after 3 weeks of force application (P = 0.001). Histological pulp changes following extrusive and intrusive force applications for 3 days and 3 weeks show no difference from each other.

BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay.

INTRODUCTION: The role of infiltrating cells (I.C.), commonly observed in the adenoma interstitial tissue, is unknown. We tested the hypothesis that I.C. are related with BPH progression by: phenotypically characterising these cells; quantifying the expression of lymphokines and growth factors; investigating the response to Permixon (P) in a clinical study. Permixon is a lipido sterolic extract of Serenoa repens possessing pharmacological activities and widely used in the treatment of men with BPH. MATERIAL AND METHODS: A multicenter open pilot study of two parallel groups on BPH patients was carried out. They were randomized to receive either oral Permixon (P) 160 mg bid for three months or to be followed for 3 weeks without any treatment before surgery (control group C). Strict inclusion and exclusion criteria were applied to conform homogeneous groups, avoiding interferences of inflammatory drugs or others. Baseline clinical profile was almost identical in both groups in terms of age (65.7+/-5.1 vs. 67.1+/-5.8 years), IPSS (19.8+/-6.1 vs. 19.0+/-5.8), prostate volume (64.8+/-18.9 vs. 71.5+/-29.3cc), Q(max) (9.6+/-3.2 vs. 10.6+/-2.6 ml/s), and Q(L) (4.0+/-1.1 vs. 3.5+/-0.7). Surgery was ultimately performed on 29 patients (17C, 12P) by TURP or retropubic adenomectomy. Adenoma samples were routinely stained with HE and later prepared for immunohistochemical studies using CD3, CD20 and CD68 antibodies. Counting of positives cells, lymphoid aggregates and foci were done using EnVision technique and the Tech Mate processor. Cytokines, growth factors and eicosanoids were determined by Elisa kits following the manufactured recommendation. RESULTS: HISTOLOGICAL: A difference was observed in the number of lymphocytes B between C (91.4+/-44.1) and P treated (58.2+/-53.7) groups (p=0.097). BIOLOGICAL MARKERS: TNFalpha and IL-1beta were dramatically lower in the Permixon treated group. Other parameters did not show significant changes. CLINICAL: IPSS in the Permixon treated group was significantly reduced (p<0.006) from 20.0+5.9 to 14.9+3.8 after three months of treatment. COMMENTS: The BPH inflammatory hypothesis was tested in humans. Our pilot study shows a significant reduction of some inflammatory parameters in prostatic tissues of patients treated with Permixon. These biological findings justify a pharmacological effect of this drug on the inflammatory status of the adenoma. A correlation with clinical improvement was observed.

[Benign prostatic hyperplasia: biological significance of lymphohistiocytic infiltration of the adenoma]. / Hiperplasia prostática benigna: significado biológico de la infiltración celular linfohistiocitaria del adenoma.

The presence of mononuclear cells infiltrating the prostate adenoma is a morphological observation well established in the literature. However, its biological meaning is a subject of controversy. It has been postulated that it may represent a local immunological reaction contributing to the pathogenesis of prostatic adenoma. Several studies have been performed to test this hypothesis, both in humans and animals. The purpose of this review is to update available information, including our own ongoing studies. Morphological research has shown that cells infiltrating the adenoma are lymphocyte T, lymphocyte B and macrophages with a high proportion of lymphocyte T. Many of the inflammatory markers, such as lymphoquines (IL1, IL2, IL4, IL6, IL13), are elevated in the adenoma tissue as are some growth factors (EGF, TGF alpha, IFN gamma, TGF beta). The general impression is that an inflammatory process is activated in the adenoma during growth and maturing. It has also been proved that this inflammatory process could be modified with treatment and, in our case, with the lipido-sterolic extract of Serenoa Repens.

[Acute kidney failure induced by rifampicin]. / Fracaso renal agudo inducido por rifampicina.

A case of acute renal failure requiring dialysis and associated with a characteristic, fulminant clinical course following the intermittent administration of rifampicin is presented. Renal biopsy showed severe tubular injury and a mild interstitial mononuclear cell infiltrate. Withdrawal of rifampicin led to a compete resolution of renal injury. We review the literature on the pathogenesis and treatment of this syndrome and we discuss the different substrates for acute renal failure induced by rifampicin.

Hepatitis C virus RNA in kidney biopsies from infected patients with renal diseases.

Hepatitis C virus (HCV) infection has been associated with several renal pathologies, including membranoproliferative and membranous glomerulonephritis. Although the presence of HCV proteins has been reported, there are no data concerning detection of the viral RNA in renal cells from HCV-infected patients with kidney disease. In this report we analysed, by in situ hybridization, the presence of HCV RNA in renal biopsies from 10 patients who were positive for antibodies to HCV (anti-HCV) and serum HCV RNA positive, and from four patients without HCV infection, with different renal disease. HCV RNA was detected in the renal biopsies from all of the 10 HCV-infected patients. Hybridization signals were detected in the tubular and capillary endothelial cells. No hybridization signals were found in the renal biopsies of the four anti-HCV-negative patients. In conclusion, our results demonstrate that HCV RNA is common in kidney cells of patients with renal diseases who are infected with HCV. The presence of HCV RNA is not necessarily associated with a pathogenetic consequence.

Histopathology of cutaneous reaction to granulocyte colony-stimulating factor: another pseudomalignancy.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor (HGF) with many applications in cancer therapy. The most important applications are reduction in the incidence of febrile neutropenia, acceleration of neutrophil recovery after chemotherapy or bone marrow transplantation, and mobilization of progenitor cells. Many cutaneous adverse reactions associated with HGF have been reported in recent years, including injection site reactions, pyoderma gangrenosum, Sweet's syndrome, cutaneous leucocytoclastic vasculitis, and widespread folliculitis. The presence of large histiocytes on the dermis between collagen bundles has been proposed as a characteristic histopathologic finding in cutaneous eruptions secondary to granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. We report on a patient with a high-risk ductal infiltrating carcinoma of the breast who received high-dose chemotherapy (HDC) with peripheral blood progenitor cell (PBPC) rescue. The patient received G-CSF after PBPC for a faster granulocyte recovery. She developed a cutaneous eruption located on back, buttocks, axillae, groin and sites where electrocardiography electrodes had been placed. From the histopathological point of view, the eruption was characterized by the presence of numerous large, atypical histiocytes in the dermis with several mitotic figures, mimicking involvement of the dermis by a malignant process.

Degos disease in a patient with acquired immunodeficiency syndrome.

Malignant atrophic papulosis is a rare disorder characterized by pathognomonic cutaneous lesions that consist of infarctive thrombosis. Visceral involvement often occurs; the gastrointestinal tract and the central nervous system are most frequently involved. Malignant atrophic papulosis has not been previously described in an AIDS patient. We describe a 58-year-old homosexual man with AIDS who developed typical cutaneous lesions of malignant atrophic papulosis. No visceral involvement has been detected in 2 years.

Cutaneous manifestations of infection by nontuberculous mycobacteria.

Cutaneous infections by nontuberculous mycobacteria (NTM) are not usual but their relative importance has changed during the last few years and still further changes are expected. This study comprised 13 patients from whom NTM were recovered from skin biopsy specimens, sinus exudates or cutaneous abscesses. All samples were processed according to standard methods, and the isolates were identified by biochemical testing. Skin biopsy specimens, when available, were processed for histopathological study. The clinical records of the patients were reviewed, and the relevant clinical, microbiological and epidemiological data collected. The clinical manifestations were noted to be relatively nonspecific and consisted of draining sinuses, abscesses, ulcers and nodules with multicentric or sporotrichoid patterns. Tissue culture isolated Mycobacterium fortuitum complex in nine patients, M. avium in three, and M. marinum in one. In the nine patients studied by histopathology, various patterns were observed. These included dermo-hypodermal abscesses, suppurative granulomas, tuberculoid granulomas and granulomas with a perifollicular distribution. Cutaneous lesions can thus be the first and the only sign of NTM disease, and culture still remains the definitive diagnostic procedure.

Interferon-inducible protein-10 is highly expressed in rats with experimental nephrosis.

Interferon-inducible protein (IP)-10 is a small glycoprotein member of a family of chemotactic cytokines structurally related to interleukin-8. We have recently described the induction of IP-10 mRNA in mouse mesangial cells stimulated with lipopolysacharide, interferon-gamma, and tumor necrosis factor-alpha. To further evaluate a possible role for this chemokine in renal injury, we have studied IP-10 in an experimental model of nephrosis induced in rats by adriamycin. High levels of glomerular IP-10 mRNA expression and glomerular and tubulointerstitial IP-10 protein were seen on day 21, coinciding with maximal proteinuria, glomerular tumor necrosis factor mRNA expression, and interstitial cellular infiltrates. Maintenance on a low protein diet not only delayed the appearance of proteinuria and interstitial cellular infiltrate but also decreased glomerular IP-10 mRNA expression. Isolated normal glomeruli and cultured glomerular epithelial and mesangial cells from normal rats expressed IP-10 mRNA upon stimulation with 100 U/ml interferon or 1 microgram/ml lipopolysaccharide for 3 hours. IP-10 mRNA expression was also inducible by lipopolysaccharide and cytokines in NRK 49F renal interstitial fibroblasts and, to a lesser extent, in NRK 52E tubular epithelial cells. Furthermore, IP-10 protein was inducible in murine mesangial cells. We conclude that IP-10 is highly inducible in vitro and in vivo in resident glomerular and tubulointerstitial cells. IP-10 may participate in the modulation of renal damage in experimental nephrosis.

Cutaneous tuberculosis: a clinical, histopathologic, and bacteriologic study.

BACKGROUND: In recent years cutaneous infections with Mycobacterium tuberculosis with an atypical clinical appearance have become more common because of the increasing number of immunocompromised patients. OBJECTIVE: We report the clinical, histopathologic, and bacteriologic data of 11 patients with several forms of cutaneous tuberculosis seen during the past 14 years. METHODS: Patients from whom M. tuberculosis was isolated from culture of skin biopsy specimens, sinus drainage, or material aspirated from cutaneous abscesses were included. In all but two patients a biopsy specimen was obtained for histopathologic study. All but one patient received combined antituberculous therapy. RESULTS: The clinical diagnoses were scrofuloderma (four cases), cutaneous miliary tuberculosis (two), lupus vulgaris (two), tuberculous gumma (two), and one unclassified. All but three patients had evidence of either previous or simultaneous tuberculous foci other than in the skin. Histopathologic findings varied according to the type of cutaneous tuberculosis. CONCLUSION: In some patients with cutaneous tuberculosis, lesions are atypical in appearance because of immunodeficiency. Culture for M. tuberculosis should be performed in all suspected cases, even in those in whom special stains for acid-fast bacilli are negative.

Malignant hidroacanthoma simplex. A case report and literature review.

A 73-year-old woman with a malignant hidroacanthoma simplex on her right lower limb is reported. The lesion was immunohistochemically studied. Carcino-embryonic antigen and epithelial membrane antigen were found in the luminal border of ductal structures within the aggregations of neoplastic cells. We review the literature on this subject.

Giant trichoblastoma on the scalp.

We describe a case of giant trichoblastoma that had been present for many years on the scalp of a 69-year-old man. The specimen was examined histopathologically, immunohistochemically, and ultrastructurally. Histopathologic examination showed that neoplastic cells were arranged in different patterns from area to area, including rippled, adenoid, and palisading patterns. In some areas of the neoplasm, foci of sebaceous differentiation were also present. The ultrastructural characteristics of neoplastic cells support the notion that trichoblastomas are neoplasms composed mostly of follicular germinative cells.

[Calciphylaxis in chronic renal failure]. / Calcifilaxis en la insuficiencia renal crónica.

Three cases of calciphylaxis in patients with terminal renal insufficiency are discussed. The existence of metastatic calcifications, mainly vascular, in patients with chronic renal insufficiency is frequent. However calciphylaxis is a process which is rarely found in these patients. This entity is characterized by the obliteration of small vessels with ischemia and necrosis. The exceptionality of the disease, its difficult treatment and poor evolution make calciphylaxis a bad prognostic complication which should be considered in the differential diagnosis of cutaneous lesions in patients with chronic renal insufficiency.